EMORY UNIVERSITY

A major challenge in vaccinology is that the efficacy of a vaccine can only be ascertained retrospectively, upon infection. The identification of molecular signatures induced rapidly after vaccination, which correlate with and predict, the later development of protective immune responses, would represent a strategy to prospectively determine vaccine efficacy. Such a strategy would be particularly useful when evaluating the efficacy or immunogenicity of untested vaccines, or in identifying individuals with sub-optimal responses amongst high risk populations such as infants or the elderly. We have recently used a systems biology approach to identify early gene signatures that correlate with, and predict the later immune responses in humans vaccinated with the live attenuated yellow fever vaccine YFV-17D. The goal of the present application is to determine extent to which such an approach will have broad utility in predicting the immunogenicity of vaccines, and help discover new correlates of protective immunity. To achieve this goal we have initiated a highly collaborative effort to perform a detailed cellular and molecular characterization of immune responses induced by three distinct vaccines: (i) the T-dependent inactivated trivalent influenza vaccine, (ii) the T-independent pneumococcal polysaccharide vaccine 23 and (iii) the live attenuated varicella-zoster vaccine. These three vaccines were selected for this study because influenza virus, pneumococcus and zoster, are of global public health importance and the cause of severe morbidity and mortality, especially in the elderly and other high-risk groups . In addition, all three of these vaccines are known to generate sub-optimal immune responses in a substantial proportion of elderly vaccinees. Defining the innate signatures in these sub-optimal responders may provide insight into the defects that underlie poor vaccine efficacy and immunogenicity in the elderly. The program is organized into two Research Projects: 1. Innate signatures (Pulendran), and 2. Adaptive Immunity (Ahmed). This research will be supported by an Adminstrative Core (Pulendran), a Clinical Research Core (Mulligan), an Epitope Mapping Core (Sette), and a Genomics & Computational Core (Haining). In addition, there will be a Pilot Project Core. The successful completion of this program may provide insights into the defects that underlie poor vaccine efficacy in the elderly, and establish the broad utility of systems biology in predicting vaccine immunogenicity.

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